Cancer associated fibroblast drives spheroid formation and pleural dissemination in non-small cell lung cancer

Pleural dissemination in non-small cell lung cancer (NSCLC) refers to cancer cells directly spreading from the primary tumor to the extrapulmonary thoracic cavity, where they colonize the pleura. This study investigated the impact of cancer-associated fibroblasts (CAFs) on the development of pleural dissemination in NSCLC. Using in vitro coculture and in vivo pleural dissemination models, we found that CAFs led to pleural dissemination by promoting cancer cell migration, anchorage-independent growth, adhesion, invasion, and spheroid formation. RNA-seq analysis revealed that CAFs upregulated the expression of the matricellular protein cellular communication network factor 1 (CCN1) in cancer cells. Subsequently, we confirmed that CCN1-overexpressing lung cancer cell lines exhibited enhanced migratory and adhesive properties in vitro and increased tumorigenicity in the thoracic cavity in the mouse model of pleural dissemination. These findings demonstrated that CAFs drive pleural dissemination by inducing spheroid formation and upregulating CCN1 expression in NSCLC.